Disease Expression in Patients with USH2A Mutations

Abstract

Abstract: : Purpose: To compare disease severity in patients with nonsyndromic versus syndromic USH2A mutations. Methods: The ocular function of 156 patients (72 males and 84 females, ages 13 to 83 years) with USH2A mutations was studied. Twenty–two patients (14%) had 2 identified mutations and the remainder had only 1 identified mutation. Fifty–four patients (35%) had 1 or 2 C759F mutations, the only mutation presently associated with nonsyndromic disease (i.e., no hearing loss). Disease severity was evaluated by comparing log Snellen visual acuity and log Goldmann kinetic visual field area (V4e stimulus) to category of mutation adjusting for age and by comparing log 30 Hz (cone) electroretinogram (ERG) amplitude to category of mutation adjusting for age and refractive error based on the first visit for which data were available. Results: The geometric mean visual acuity was comparable (p = 0.51) in patients with the C759F mutation (20/32) and without that mutation (20/34). The geometric mean visual field area was larger in patients with the C759F mutation (3718 square degrees) than in those without that mutation (2899 square degrees), but the difference was not significant (p = 0.32). However, patients with the C759F mutation had a geometric mean cone ERG amplitude (2.3 µV) that was significantly larger (p < 0.001) than that of patients without this mutation (0.9 µV). Conclusions: Based on cone ERG amplitude, patients with the C759F USH2A mutation associated with nonsyndromic disease on average appear to have a milder form of photoreceptor degeneration than USH2A patients without this mutation.

Keywords: retinal degenerations: hereditary • electroretinography: clinical • gene/expression